Table 1.
Features of the studies published on SGLT2-I effects on NAFLD patients.
| Author/Year | Design/Duration | Drug | Posology | Outcome(s) | Conclusion |
|---|---|---|---|---|---|
| Ohki T, et al., [86] 2016; |
Observational (retrospective) 45 weeks median Patients n° 24 |
Ipragliflozin | Ipragliflozin 50 mg + DPP-4I (n° 13) vs. Ipragliflozin 50 mg + GLP-1 RA (n° 11) |
Changes ALT levels and body weight at the end of the follow-up | Ipragliflozin normalizes ALT levels and improves glycemic control, it reduces body weight, FIB-4 score, in patients who did not respond to incretin-based therapy |
| Seko Y, et al., [94] 2016; |
Observational (retrospective) 24 weeks Patients n° 45 |
DPP4-I vs. SGLT2-I |
Sitagliptin 100 mg daily (n° 21) vs. Canagliflozin 100 mg daily or ipragliflozin 50 mg daily (n° 24) |
Correlation between changes in aminotransferase, body weight, glycemic control, and HbA1c | The reductions in ALT and HbA1c were similar between SGLT2-I and DPP4-I groups, whereas body weight was significantly reduced in the SGLT2-I group compared with the DPP4-I group |
| Ito D, et al., [85] 2017; |
RCT, OL, single center 24 weeks Patients n° 66 |
Ipragliflozin vs. Pioglitazone |
Ipragliflozin 50 mg daily (n° 32) vs. Pioglitazone 15–30 mg daily (n° 34) |
Change from baseline in L/S ratio on CT | Both had benefits on NAFLD and glycemic control; Ipragliflozin reduced body weight and abdominal fat area |
| Kuchay MS, et al., [82] 2018; E-LIFT Trial |
RCT, OL, single center. 20 weeks Patients n° 50 |
Empagliflozin vs. ST T2DM |
Empagliflozin + ST T2DM (n° 25) vs. ST T2DM (n° 25) |
Change in liver fat was measured by MRI-PDFF. Secondary outcome measures were change in ALT, AST, and GGT levels | Empagliflozin reduces liver fat and improves ALT levels in patients |
| Shimizu M, et al., [84] 2018; |
RCT, OL, single center. 24 weeks Patients n° 57 |
Dapagliflozin vs. ST T2DM |
Dapagliflozin 5 mg daily (n° 33) vs. ST T2DM (n° 24) |
HS and fibrosis were assessed using transient elastography to measure CAP and liver stiffness, respectively | Dapagliflozin improves HS and attenuates liver fibrosis in patients with significant liver fibrosis |
| Gautam A, et al., [91] 2018; |
Observational. 24 weeks Patients n° 31 |
Canagliflozin + ST T2DM |
Canagliflozin 100 mg daily + ST T2DM |
Improves LFT and HbA1c | Canagliflozin controls HbA1c and reduce weight in type 2 diabetes, and significantly improves LFT |
| Shibuya T, et al., [93] 2018; |
RCT, OL, single center, prospective. 24 weeks Patients n° 32 |
Luseogliflozin vs. Metformin |
Luseogliflozin 2.5 mg daily (n° 16) vs. Metformin 1500 mg daily (n° 16) |
Change in L/S ratio obtained by CT |
Luseogliflozin significantly reduces liver fat deposition compared to metformin |
| Sumida Y, et al., [92] 2019; |
Prospective, 24 weeks Patients n° 40 |
Luseogliflozin + ST T2DM | Luseogliflozin 2.5 mg once daily + ST T2DM (without insulin) |
Change in HbA1c and hepatic fat content from baseline. The secondary endpoints were the changes: routine liver biochemistries, blood pressure, lipid profiles, and hepatic fibrosis markers | Improves HbA1c, transaminase levels, and hepatic fat content |
| Akuta N, et al., [88] 2019; |
Prospective, OL, single center. 24 weeks Patients n° 9 |
Canagliflozin | Canagliflozin 100 mg daily | Histological improvement, defined as a decrease in NAFLD activity score without worsening in fibrosis stage | All patients achieved histological improvement. Scores of steatosis, lobular inflammation, ballooning, and fibrosis stage decreased at 24 weeks |
| Inoue M, et al., [89] 2019; |
Prospective, OL, single center. 48 weeks Patients n° 20 |
Canagliflozin + ST T2DM |
Canagliflozin 100 mg daily + ST T2DM |
Change in body composition measured by bioelectrical impedance analysis method and hepatic fat fraction measured by MRI | Canagliflozin reduced body mass, fat mass, and hepatic fat content without significantly reducing muscle mass |
| Kahl S, et al., [83] 2020; |
RCT, prospective, multi center. 24 weeks Patient n° 84 |
Empagliflozin vs. Placebo |
Empagliflozin 25 mg daily (n° 42) vs. Placebo (n° 42) |
Change in liver fat content measured with MRI | Empagliflozion reduces hepatic fat with excellent glycemic control and short known disease duration |
| Han E, et al., [87] 2020; |
RCT, OL, single center. 24 weeks Patient n° 44 |
Metformin + Pioglitazone + Ipragliflozin vs. Metformin + Pioglitazone |
Ipragliflozin 50 mg daily (n° 29) + Metformin + Pioglitazone vs. Metformin + Pioglitazone (n° 19) |
Change in HS measured by fatty liver index, NAFLD liver fat score, and CAP | Ipragliflozin improves liver steatosis and reduces excessive fat in euglycemic patients |
| Nishimiya N, et al., [90] 2021; |
Prospective, single center 24 weeks Patient n° 9 |
Canagliflozin + ST T2DM |
Canagliflozin 100 mg daily + ST T2DM |
Change in HS assessed using the hepatic MRI-PDFF | Canagliflozin improved HS reducing adiposity, insulin resistance, inflammation, and skeletal muscle volume |
ALT: alanine aminotransferase; AST: aspartate aminotransferase; CAP: controlled attenuated pressure; CT: computed tomography; DPP4-I: dipeptidyl peptidase-4 inhibitor; FIB-4: Fibrosis-4 score; GGT: gamma-glutamyl transferase; GLP1-RA: glucagon-like peptide 1 receptor agonist; HS: hepatic steatosis; LFT: liver function test; L/S ratio: liver-to-spleen attenuation ratio; MRI-PDFF: magnetic resonance imaging estimated proton density fat fraction; NAFLD: non-alcoholic fatty liver disease; OL: open label; RCT: randomized controlled trial; SGLT2-I: sodium glucose cotransporter-2 inhibitors; ST: standard treatment; T2DM: type 2 diabetes mellitus.